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PONE-D-21-25385Prevalence and Correlates of SARS-CoV-2 Seropositivity among People who Inject Drugs in the San Diego-Tijuana Border RegionPLOS ONE

Dear Dr. Strathdee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Additional Editor Comments (if provided):

Reviewers indicate several areas that can strengthen this manuscript. Although they differ in their suggestions regarding - minor and major revision, I do think that the comments from both are helpful and appropriate and can be easily addressed. I do disagree that the 'a priori' note needs to be removed. I think this is a good manuscript and hope the authors will revise and resubmit. 

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Kimberly Page, PhD, MPH

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript makes an important contribution to the COVID literature among the PWID population with high rates of sex work. One important finding is that injection drug use or other substance use behaviors were not associated with seroprevalence; rather circumstances in the risk environment, notably sex work and incarceration, were associated with significantly higher SARS-CoV-2 seroprevalence.

Several clarification and suggestions are below:

• Clarification on recruitment: The authors indicated that street-based recruiting was used between October 28, 2020 and June 16, 2021 (a period when the border was closed to essential travel). It’s unclear how recruitment was done for participants in Tijuana and “those from either city who reported not having used illicit drugs on the other side of the border”. Was all recruitment done in San Diego?

• Clarification needed on “personal interviewing” – were individuals interviewed in person during this period? Or via Zoom?

• Did the study collect identifiers in order to ascertain duplicate enrollments?

• In the limitations section, the authors reported the majority of participants had IgM; however, this is not reported in the results. Given that there were no active infections reported in the sample, it would be interesting to report how many (if any) were individuals had only IgM and not IgG as an estimate of recent infection.

• Minor: The recruitment period includes a few months where individuals may have gotten vaccinations. While most antibody tests were not designed to specifically detect antibodies as a result of vaccination, is the possible that particular antibody tests used may have yielded a false positive? This would be easily seen if the 9 individuals who reported if the participant were all positive relative to the rest of the sample. In the limitations section, the authors reported on the vaccinated portions of the sample, but not in the results. Nonetheless, the authors did report that excluding nine participants who reported having received at least one COVID-19 vaccine did not appreciably change parameter estimates in multivariable analysis.

• Minor Suggestion: Table 1 reports column %, which provide snapshot of the sample distribution. It would be interesting to more directly compare sub-groups (row%). One suggestion would be just to the univariate RR from Table 2 to Table 1.

Reviewer #2: Thank you for giving me the opportunity to review the manuscript titled “Prevalence and Correlates of SARS-CoV-2 Seropositivity among People who Inject Drugs in the San Diego- Tijuana Border Region.” This manuscript presents relevant information related to the prevalence and correlates of SARS-CoV-2 in PWID, a vulnerable population at increased risk for infection and increased morbidity and mortality. This study is innovative in terms that it provides novel information related to PWID living in an understudied region and at an increased vulnerability. However, there are some issues in this paper that limit my enthusiasm.

Introduction

Overall, this section is extremely short and does not provide the background necessary to understand why this research study exploring the prevalence and correlates of SARS-CoV-2 among people who inject drugs is necessary.

I recommend including estimates and correlates of SARS-CoV-2 obtained from earlier studies involving people with substance use disorder. I would also suggest including the limitations in earlier research studies (e.g., mostly conducted in developed countries), which would strengthen the Introduction section.

The Introduction section should highlight the fact that SARS-CoV-2 could be a serious threat to health among those people who use drugs.

There is not a lack of data on the effects of SARS-CoV-2 on people with substance use disorders. In fact, there is a growing amount of research focusing on this topic. It would be important to reframe the second sentence and specify in which specific area lacks data.

Methods

There are several aspects related to the study procedures that are ambiguous. The order of the assessments is unclear. It would be very helpful to include a paragraph describing the order of the assessments.

The inclusion criteria are unclear for participating in this study. It is presented that individuals who recently injected any drugs (within 30 days) are eligible, but also those who injected drugs in the last two years as well as those who reported not having used illicit drugs. I would recommend listing the inclusion and exclusion criteria to improve readability.

Did the participants provide written informed consent?

It would be important to cite where the questionnaire came from.

Participants self-collected nasal swabs. Were these participants trained in the use of the swabs to ensure they were collecting the biological samples correctly?

There is no description of when and by whom the SARS-CoV-2 antibody, HIV, and HCV serology tests were conducted.

Data analyses

It would be interesting to explore whether the characteristics of the participants with inconclusive SARS-CoV-2 results differ from those with positive results.

Results

I suggest some editing in this section to improve readability. It would be helpful to focus one paragraph only describing the overall sample, then another presenting the bivariate analyses, and a final one describing the multivariate analyses.

Discussion

This section provides information that would have been useful in the Introduction section to provide a background on the topic. This includes the prevalence and correlates of SARS-CoV-2.

This section presents 7 different findings obtained from the current study. It is unclear what the take home message is. I would suggest rewording and reorganizing this section to focus on the most relevant findings.

It should be noted that the reasons for these 7 different findings are not fully described.

Recent or past drug use is self-reported. This should be included as a study limitation.

Conclusions

The conclusions section does not fully mirror what is presented in the Discussion section and reads as a different paper. This last paragraph should focus on the findings related to the prevalence of SARS-CoV-2 and its correlates among PWID. The additional information is distracting.

Minor comments:

- Remove “a priori” from the sentence “We hypothesized a priori that…”

- Include the software used to conduct the data analyses

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Reviewer #1: No

Reviewer #2: Yes: Irene Pericot-Valverde

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Prevalence and Correlates of SARS-CoV-2 Seropositivity among People who Inject Drugs in the San Diego-Tijuana Border Region

PONE-D-21-25385R1

Dear Dr. Strathdee,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Kimberly Page, PhD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: